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Son C, Kalapala J, Leya J, Popadiuk MM, Atieh MK, Havlichek D, Feldman L, Roach P, Banerjee P. Gastroesophageal Neuroendocrine Tumors: Outcomes and Management. J Clin Med 2025; 14:2148. [PMID: 40217599 PMCID: PMC11989656 DOI: 10.3390/jcm14072148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Revised: 03/14/2025] [Accepted: 03/15/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: Neuroendocrine tumors (NETs) can arise in any organ and are most commonly found in the lungs and gastroenteropancreatic (GEP) system. GEP-NETs represent a small percentage of gastrointestinal cancers, and therefore, the standard treatment is not well-defined, especially for advanced disease. Our objective is to review GI NETs among veterans and analyze their therapeutic outcomes. Methods: A total of 61 GI NET cases were identified from our institution from 2019-2024. In total, twenty-seven review papers, ten population-based/multicenter/outcome studies, six case reports, and one case series were reviewed for the literature review. Results: The incidence of GI NETs at our institution was higher than the known epidemiology of GI NETs. Small intestine NETs were one of the most common sites of GEP-NETs at our institution, with only one of nineteen cases being grade 3 poorly differentiated neuroendocrine carcinoma. All cases of colonic and rectal NETs had good clinical outcomes consistent with findings from the literature. Most of the gastric NETs were type 1 and had benign courses of disease, except for one case with an intermediate grade and metastatic liver lesions. One case of esophageal neuroendocrine carcinoma (E-NEC) showed a complete response to chemotherapy despite a significant tumor burden on presentation and high-grade pathology, while another case of ENEC had recurrent disease despite systemic therapy. Conclusions: While the role of surgery or endoscopic resection is limited to localized tumors, combined treatment with chemoradiation can significantly improve patient outcomes, especially in high-grade, poorly differentiated tumors. Further studies are needed to establish systemic (i.e., chemotherapy and radiation) treatment strategies for poorly differentiated GI NETs.
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Affiliation(s)
- Christine Son
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
- Loyola Internal Medicine, University Medical Center, Maywood, IL 60153, USA
| | | | - Jeff Leya
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
| | - Michelle Marion Popadiuk
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
| | - Mohammed K. Atieh
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
- Loyola Internal Medicine, University Medical Center, Maywood, IL 60153, USA
| | - Daniel Havlichek
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
- Loyola Internal Medicine, University Medical Center, Maywood, IL 60153, USA
| | - Lawrence Feldman
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
- UI Health, University of Illinois in Chicago Hospital Health Sciences System, UIC Medical Center, Chicago, IL 60612, USA
| | - Paul Roach
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
| | - Promila Banerjee
- Edward Hines VA Hospital, Hines, IL 60141, USA; (J.L.); (M.M.P.); (M.K.A.); (L.F.); (P.R.); (P.B.)
- Loyola Internal Medicine, University Medical Center, Maywood, IL 60153, USA
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Hong Q, Wu K, Chen C, Dang Y, Zhang Q, Zhang X, Wang L, Han R, Zhao C, Yi H, Li F, Zhang R, Mu J, Li J. Characterizing esophageal mixed neuroendocrine-non-neuroendocrine neoplasms: insights from a retrospective multicenter study of clinical outcomes and prognostic indicators. Ther Adv Med Oncol 2024; 16:17588359241303066. [PMID: 39649016 PMCID: PMC11624530 DOI: 10.1177/17588359241303066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 11/11/2024] [Indexed: 12/10/2024] Open
Abstract
Background The esophageal mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is an extremely rare but poor prognosis tumor. Objectives This retrospective study aimed to analyze the clinical characteristics of MiNEN and to investigate postoperative survival and prognostic factors. Design This retrospective study analyzed 69 patients diagnosed with esophageal MiNEN at two major esophageal cancer centers in China from January 2000 to December 2021. Methods We assessed demographic data, tumor characteristics, treatment modalities, and survival outcomes. Statistical analyses included Kaplan-Meier survival curves and Cox regression models to evaluate prognostic factors. Results The most common histological types were combinations of small-cell carcinoma and squamous carcinoma (91.3%). The correct diagnostic rate of preoperative pathologic biopsy was only 4.3%. The median overall survival (OS) was 24.0 months, and disease-free survival (DFS) was 16.6 months. The 1-, 3-, and 5-year survival rates were 84.1%, 34.8%, and 25.3%, respectively. A peak period of recurrence or metastasis occurs in the first year after surgery, and regional lymph node recurrence is the main route of postoperative recurrence or metastasis. Tumor size, T-stage, N-stage, and tumor, lymph node, metastasis (TNM) stage were significant prognostic factors. Subgroup analyses showed that in patients with limited-stage MiNEN in stages I-III, the postoperative adjuvant treatment modality failed to improve OS and DFS compared with surgery alone. Postoperative adjuvant therapy also failed to prolong OS and DFS in patients with lymph node-positive MiNEN. No significant survival benefits were observed with different surgical techniques or adjuvant chemotherapy regimens. Conclusion Esophageal MiNEN has aggressive behavior and a poor prognosis. In China, the pathologic type of esophageal MiNEN may be dominated by a combination of small-cell carcinoma and squamous carcinoma. Early-stage disease significantly correlated with improved survival outcomes. Current treatment protocols, similar to those for other esophageal cancers, show limited efficacy in improving patient survival.
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Affiliation(s)
- Qian Hong
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Kaiming Wu
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Chen Chen
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Dang
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Qiuju Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xue Zhang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Liting Wang
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rui Han
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenguang Zhao
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hang Yi
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fang Li
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Renquan Zhang
- Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Ji Xi Road, Hefei 230000, Anhui, China
| | - Juwei Mu
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China
| | - Jiagen Li
- Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17, Panjiayuan Nanli, Chaoyang District, Beijing 100021, China
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3
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Sun H, Shi Y, Liang D, Liu J, Xu G, Yang X. Esophageal mixed or collision small cell-squamous cell carcinoma: Report of 6 cases and review of the literature. Indian J Cancer 2024; 61:759-765. [PMID: 39960705 DOI: 10.4103/ijc.ijc_173_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 10/14/2021] [Indexed: 03/17/2025]
Abstract
BACKGROUND Esophageal mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs) are now known as a neuroendocrine component mixed with a nonneuroendocrine component in a single neoplasm, one of which is in the form of mixed small cell-squamous cell carcinoma. Collision tumors have been excluded from the category of MiNENs, but difference between mixed and collision small cell-squamous cell carcinoma has never been reported. METHODS We collected six cases and reviewed 11 cases of mixed or collision small cell-squamous cell carcinoma (MCSSC); the data from 17 cases of MCSSC were analyzed to observe their clinicopathological features. RESULTS Most of the MCSSC patients were middle-aged and elderly, with more men than women, and most of the tumors occurred in the middle and lower esophagus. We found that in mixed cancers, the metastases were a mixture of squamous cell carcinoma and small cell carcinoma, whereas metastatic foci in collisional tumors showed simple cancer components; this phenomenon has never been reported before. Mixed cancers account for a higher proportion of small cell carcinomas, a higher pathological stage, and a worse prognosis than collisional cancers. PD-L1 (22C3) was negative in both squamous cell carcinoma and small cell carcinoma regions (<1%). CONCLUSIONS Mixed and collisional small cell-squamous cell carcinomas are essentially distinct tumors. In the clinical diagnostic of MCSSC, the tumor should be clearly identified as mixed or collisional carcinoma to guide the clinical treatment and prognosis more accurately.
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Affiliation(s)
- Huajun Sun
- Department of Pathology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Department of Pathology, University of Electronic Science and Technology of China, Chengdu, China
| | - Yanfen Shi
- Department of Pathology, China-Japan Friendship Hospital, Beijing, China
| | - Dongni Liang
- Department of Pathology, The Second Affiliated West China Hospital of Sichuan University, Chengdu, China
| | - Juan Liu
- Department of Pathology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Department of Pathology, University of Electronic Science and Technology of China, Chengdu, China
| | - Gang Xu
- Department of Pathology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Department of Pathology, University of Electronic Science and Technology of China, Chengdu, China
| | - Xudan Yang
- Department of Pathology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Department of Pathology, University of Electronic Science and Technology of China, Chengdu, China
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Hou T, Yang Z, Zhang Q, Zhang X, Liao X, Lin J. Histology Shift in Esophageal Cancer Between Biopsies and Resections After Neoadjuvant Therapy: A Pilot Study. Int J Surg Pathol 2024; 32:920-925. [PMID: 37899731 DOI: 10.1177/10668969231208029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2023]
Abstract
Preoperative neoadjuvant therapy followed by resection is the mainstay treatment for locally advanced esophageal adenocarcinoma. We recently observed the histology shift from predominant esophageal adenocarcinoma in the biopsy to neuroendocrine neoplasm with or without adenocarcinoma in the post-treatment resection. The underlying mechanism of this finding is uncertain, and there is limited information in the literature. A total of 11 patients were identified: 10 patients received presurgical chemoradiation and 1 with chemotherapy. All biopsies were diagnosed with adenocarcinoma. When neuroendocrine immunomarkers were retrospectively performed on 5 biopsies, 2 showed focal positivity, although the classic neuroendocrine morphology was not readily appreciated. All resections contained neuroendocrine neoplasm, including 8 of well-differentiated type and 3 of neuroendocrine carcinomas. Two post-treatment esophagectomies consisted of neuroendocrine neoplasm only without residual adenocarcinoma. Upon follow-up, 8 patients died of the disease (median survival = 26 months), and 3 patients were alive after a median follow-up of 14 months. The overall median survival time was better than the reported esophageal neuroendocrine carcinoma (15 months). The 5-year observed survival rate was 11.3%, which was lower than the Surveillance, Epidemiology, and End Results 5-year survival rate of adenocarcinoma (21.8%). We reported a small series of esophageal adenocarcinoma that showed histology shift between biopsy and esophagectomy after neoadjuvant therapy. Our limited data suggest that prognosis of this group is different than the conventional adenocarcinoma. Awareness of this morphological change reminds pathologists to examine the biopsy specimens thoroughly, because recognition of neuroendocrine neoplasm, especially high-grade neuroendocrine component, might potentially affect pre- and post-surgical regimens.
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Affiliation(s)
- Tieying Hou
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Zhaohai Yang
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Qingzhao Zhang
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Xuchen Zhang
- Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
| | - Xiaoyan Liao
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Jingmei Lin
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
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Alamin F, Sage H, Torres I, Parikh J, Zayat V. Unveiling the Rarity: A Case of a Mixed Neuroendocrine-Non-Neuroendocrine Tumor of the Gastroesophageal Junction. Cureus 2024; 16:e63141. [PMID: 39055477 PMCID: PMC11272183 DOI: 10.7759/cureus.63141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/24/2024] [Indexed: 07/27/2024] Open
Abstract
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are a rare group of heterogeneous tumors, consisting of an endocrine and a nonendocrine component, which can develop throughout the gastrointestinal (GI) tract. This case presents a 70-year-old man with a complex medical history who initially presented with an upper GI bleed. After being stabilized, he underwent an esophagogastroduodenoscopy (EGD) that revealed a suspicious gastroesophageal junction (GEJ) mass. Histopathological studies paired with immunohistochemical investigations of the mass confirmed the rare diagnosis of MiNENs. He then underwent an endoscopic submucosal dissection (ESD) with subsequent chemotherapy and adjunct radiotherapy, with no recurrence noted on post-treatment surveillance. This case highlights the need for an EGD, histopathological examination, and immunohistochemical staining for detecting the underlying etiology of an upper GI bleed.
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Affiliation(s)
- Faris Alamin
- Internal Medicine, University of Central Florida/HCA Osceola Hospital, Orlando, USA
| | - Hannah Sage
- Pathology, University of Central Florida College of Medicine, Orlando, USA
| | - Isabel Torres
- Pathology, University of Central Florida College of Medicine, Orlando, USA
| | - Jignesh Parikh
- Pathology, Orlando Veterans Affairs Medical Center, Orlando, USA
| | - Vania Zayat
- Pathology, Orlando Veterans Affairs Medical Center, Orlando, USA
- Pathology, University of Central Florida College of Medicine, Orlando, USA
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Esposito I, Häberle L, Yavas A. Neuroendokrine Neoplasien. DIE GASTROENTEROLOGIE 2024; 19:202-213. [DOI: 10.1007/s11377-024-00784-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 03/12/2024] [Indexed: 01/06/2025]
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Díaz-López S, Jiménez-Castro J, Robles-Barraza CE, Ayala-de Miguel C, Chaves-Conde M. Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract. World J Gastrointest Oncol 2024; 16:1166-1179. [PMID: 38660639 PMCID: PMC11037054 DOI: 10.4251/wjgo.v16.i4.1166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 01/17/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.
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Affiliation(s)
- Sebastián Díaz-López
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | | | | | - Carlos Ayala-de Miguel
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
| | - Manuel Chaves-Conde
- Medical Oncology Department, Hospital Universitario Valme, Seville 41014, Andalucía, Spain
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8
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Cheng YQ, Wang GF, Zhou XL, Lin M, Zhang XW, Huang Q. Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report. World J Gastrointest Oncol 2024; 16:563-570. [PMID: 38425401 PMCID: PMC10900165 DOI: 10.4251/wjgo.v16.i2.563] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/09/2023] [Accepted: 01/04/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma (NEC) component arising in the gastroesophageal junctional (GEJ) region is rare and even rarer in young patients. Here, we report such a case in a 29-year-old Chinese man. CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation. Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line, without Barrett's esophagus or involvement of the gastric cardia. The nodule was completely resected by endoscopic submucosal dissection (ESD). Pathological examination confirmed diagnosis of intramucosal adenocarcinoma mixed with an NEC component, measuring 1.5 cm. Immunohistochemically, both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%; NEC was positive for synaptophysin and chromogranin. Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene, a common gastric cancer driver gene, in addition to pathogenic somatic mutations in P53 and CHEK2 genes. The patient was alive without evidence of the disease 36 mo after ESD. CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.
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Affiliation(s)
- Yu-Qing Cheng
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213164, Jiangsu Province, China
| | - Geng-Fang Wang
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213164, Jiangsu Province, China
| | - Xiao-Li Zhou
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213164, Jiangsu Province, China
| | - Min Lin
- Gastroenterology Center, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213164, Jiangsu Province, China
| | - Xin-Wen Zhang
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213164, Jiangsu Province, China
- Graduate School, Dalian Medical University, Dalian 116044, Liaoning Province, China
| | - Qin Huang
- Department of Pathology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213164, Jiangsu Province, China
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, United States
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Sharobim M, Matkovic E, Schwalbe M, Matkowskyj KA. Pathologic Features of Miscellaneous Foregut Malignancies. Cancer Treat Res 2024; 192:49-66. [PMID: 39212915 DOI: 10.1007/978-3-031-61238-1_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Neuroendocrine neoplasms are a heterogeneous group of tumors that can occur in almost any organ and share a common neuroendocrine phenotype.
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Affiliation(s)
- Mark Sharobim
- School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
| | - Eduard Matkovic
- School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
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10
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Zhong L, Pan Y, Han S, Qi Q, Liao H, Jiang Y, Shen J. The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma. Indian J Cancer 2023; 60:512-520. [PMID: 38206083 DOI: 10.4103/ijc.ijc_151_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 03/01/2021] [Indexed: 01/12/2024]
Abstract
PURPOSE The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. METHODS Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. RESULTS In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). CONCLUSIONS Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.
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Affiliation(s)
- Liping Zhong
- Department of Medical Oncology, Huzhou Central Hospital, Affiliated Central Hospital HuZhou University, Zhejiang, China
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11
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Patel P, Zaher EA, Sqour H. High-Grade Pure Esophageal Neuroendocrine Carcinoma Arising From Barrett's Mucosa: A Rare Phenomenon. Cureus 2023; 15:e40644. [PMID: 37476144 PMCID: PMC10355687 DOI: 10.7759/cureus.40644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2023] [Indexed: 07/22/2023] Open
Abstract
Esophageal neuroendocrine carcinoma (E-NEC) is a very rare neuroendocrine tumor. There are only a few case reports where pure esophageal NEC is found to be arising from Barett's mucosa. Here we present a case of high-grade pure E-NEC arising from Barrett's esophagus, which was metastasized to the liver at the time of diagnosis.
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Affiliation(s)
- Parth Patel
- Internal Medicine, Ascension Saint Joseph Hospital, Chicago, USA
| | - Eli A Zaher
- Internal Medicine, Ascension Saint Joseph Hospital, Chicago, USA
| | - Hasan Sqour
- Internal Medicine, Ascension Saint Joseph Hospital, Chicago, USA
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12
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Sugawara K, Fukuda T, Kishimoto Y, Oka D, Kawashima Y, Inoshita N, Kanda H. Combined tubular adenocarcinoma, neuroendocrine carcinoma and adenocarcinoma with enteroblastic differentiation arising in Barrett esophagus. Clin J Gastroenterol 2023:10.1007/s12328-023-01791-0. [PMID: 37027114 DOI: 10.1007/s12328-023-01791-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Accepted: 03/26/2023] [Indexed: 04/08/2023]
Abstract
Adenocarcinoma (AC) with neuroendocrine carcinoma (NEC) or enteroblastic (ENT) differentiation rarely develops in Barrett's esophagus (BE). A 76-year-old man was diagnosed with Barrett's AC (cT1bN0M0) and underwent thoracoscopic esophagectomy. A type 0-IIc + 0-Is lesion measuring 26 × 21 mm was macroscopically observed on a background of long segment BE (pT1bN0M0). The tumor comprised three different histological types of carcinoma (NEC, AC with ENT differentiation and moderately differentiated AC). NEC showed positivity for synaptophysin, chromogranin A and insulinoma-associated protein 1 with a Ki-67 index of 60.6%. ENT tumors were immunopositive for AFP and sal-like protein 4, and focally immunopositive for human chorionic gonadotrophin. The amounts of NEC, ENT and AC were 40%, 40% and 20%, respectively. p53 expression was positive throughout the tumor. Rb expression was negative at the NEC, but positive at the ENT and AC. CD4 and CD8 densities were lower in the NEC segment than in the AC and ENT segments, and PD-L1 expression was negative throughout the tumor. Early cancer arising in BE with a combination of tubular AC, ENT tumors and NEC is very rare. Our observations might contribute to understanding the carcinogenetic pathways and tumor microenvironment of NEC and ENT tumors.
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Affiliation(s)
- Kotaro Sugawara
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Takashi Fukuda
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Yutaka Kishimoto
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Daiji Oka
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Yoshiyuki Kawashima
- Department of Gastroenterological Surgery, Saitama Cancer Center Hospital, Saitama, Japan
| | - Naoko Inoshita
- Department of Pathology, Moriyama Memorial Hospital, Tokyo, Japan
- Department of Pathology, Saitama Cancer Center Hospital, 780 Komuro Inamachi, Kitaadachi-Gun, Saitama, 362-0806, Japan
| | - Hiroaki Kanda
- Department of Pathology, Saitama Cancer Center Hospital, 780 Komuro Inamachi, Kitaadachi-Gun, Saitama, 362-0806, Japan.
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13
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Hou G, Zhao N, Li F, Jing H, Zheng R. Prognostic value of pretreatment 18F-FDG PET/CT metabolic parameters in esophageal high-grade neuroendocrine carcinoma: A bicenter retrospective study. Front Oncol 2023; 13:1145557. [PMID: 36994200 PMCID: PMC10042323 DOI: 10.3389/fonc.2023.1145557] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 02/27/2023] [Indexed: 03/14/2023] Open
Abstract
ObjectiveThe aim of this bicentric retrospective study was to assess the prognostic value of 18F-FDG PET/CT in patients with esophageal high-grade neuroendocrine carcinoma (NECs).MethodsFrom the database of two centers, 28 patients affected by esophageal high-grade NECs who underwent 18F-FDG PET/CT before treatment were retrospectively reviewed. Metabolic parameters (SUVmax, SUVmean, tumor-to-blood-pool SUV ratio (TBR), tumor-to-liver SUV ratio (TLR), metabolic tumor volume (MTV), total lesion glycolysis (TLG)) of the primary tumor were measured. Univariate and multivariate analyses were performed for progression-free survival (PFS) and overall survival (OS).ResultsAfter a median follow-up period of 22 months, disease progression occurred in 11 (39.3%) patients, and death occurred in 8 (28.6%) patients. The median PFS was 34 months, and the median OS was not reached. Univariate analyses revealed that among metabolic parameters, only MTV and TLG were significant prognostic factors, while among clinical variables, only distant metastasis was a significant factor for both PFS and OS (P< 0.05). On multivariate analyses, MTV and TLG were independent prognostic factors for both PFS and OS (P< 0.05).ConclusionsIn patients with esophageal high-grade NEC, MTV and TLG measured on pretreatment 18F-FDG PET/CT are independently prognostic factors for predicting PFS and OS, and might be used as quantitative prognostic imaging biomarkers.
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Affiliation(s)
- Guozhu Hou
- Nuclear Medicine Department (PET-CT Center), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Nuclear Medicine Department (PET-CT Center), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Langfang, China
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ningning Zhao
- Department of Nuclear Medicine, Weifang People’s Hospital, Weifang, Shandong, China
| | - Fang Li
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongli Jing
- Department of Nuclear Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Rong Zheng, ; Hongli Jing,
| | - Rong Zheng
- Nuclear Medicine Department (PET-CT Center), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Nuclear Medicine Department (PET-CT Center), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Langfang, China
- *Correspondence: Rong Zheng, ; Hongli Jing,
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14
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Zhang L, Yu B, Liu Z, Wei J, Pan J, Jiang C, Li Z. Analysis of the Clinicopathological Characteristics, Prognosis, and Lymphocyte Infiltration of Esophageal Neuroendocrine Neoplasms: A Surgery-Based Cohort and Propensity-Score Matching Study. Cancers (Basel) 2023; 15:cancers15061732. [PMID: 36980618 PMCID: PMC10046526 DOI: 10.3390/cancers15061732] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 01/31/2023] [Accepted: 02/22/2023] [Indexed: 03/14/2023] Open
Abstract
Background: Esophageal neuroendocrine neoplasms (E-NENs) are a rare and poorly reported subtype of esophageal carcinoma. We analyzed the differences in clinicopathological features, prognosis, and tumor-infiltrating lymphocytes (TILs) between E-NENs and esophageal squamous cell carcinoma (ESCC). Methods: A total of 3620 patients who underwent esophagectomy were enrolled retrospectively. The study cohort was divided into two groups (E-NENs and ESCC) through propensity-score matching, and the prognosis and TILs were compared between the two groups. The TILs were assessed using tumor specimens (including six cases of ESCC, six cases of neuroendocrine carcinomas [NECs], and six cases of mixed neuroendocrine–non-neuroendocrine neoplasms [MiNENs]). Results: E-NENs accounted for 3.0% (107/3620) of cases, among which there were just 3 neuroendocrine tumor cases, 51 NEC cases, and 53 MiNENs cases. After matching, esophageal neuroendocrine carcinomas (E-NECs) showed both poorer 5-year overall survival (OS; 35.4% vs. 54.8%, p = 0.0019) and recurrence-free survival (RFS; 29.3% vs. 48.9%, p < 0.001) compared with ESCC. However, the differences were not prominent in the subgroup with stage I. No significant survival benefit was observed for E-NECs with multimodal therapy. Multivariate analysis demonstrated that E-NECs are an independent risk factor for OS and RFS. In the exploratory analysis, E-NECs were associated with less infiltration of immune cells compared with ESCC. Conclusion: E-NECs are significantly associated with a poorer prognosis than ESCC except for early-stage disease. The fewer TILs within the tumor microenvironment of E-NECs compared with ESCC results in weaker anti-tumor immunity and may lead to a poorer prognosis.
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Affiliation(s)
- Long Zhang
- Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Boyao Yu
- Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Zhichao Liu
- Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Jinzhi Wei
- Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Jie Pan
- Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Chao Jiang
- Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
| | - Zhigang Li
- Department of Thoracic Surgery, Section of Esophageal Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
- Correspondence:
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15
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Mohamed A, Wu S, Hamid M, Mahipal A, Cjakrabarti S, Bajor D, Selfridge JE, Asa SL. Management of Appendix Neuroendocrine Neoplasms: Insights on the Current Guidelines. Cancers (Basel) 2022; 15:295. [PMID: 36612291 PMCID: PMC9818268 DOI: 10.3390/cancers15010295] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/19/2022] [Accepted: 12/26/2022] [Indexed: 01/03/2023] Open
Abstract
Appendiceal neuroendocrine neoplasms (ANENs) usually present as incidental findings at the time of appendectomy for acute appendicitis. They are rare, accounting for only 0.5-1% of intestinal neoplasms; they are found in 0.3-0.9% of all appendectomy specimens. They are usually sporadic tumors. There are several histological types including well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Histologic differentiation and the grade of well-differentiated NETs correlate with clinical behavior and prognosis. Management varies based on differentiation, aggressiveness, and metastatic potential. There is debate about the optimal surgical management for localized appendiceal NETs that are impacted by many factors including the tumor size, the extent of mesoappendiceal spread, lymphovascular invasion and perineural involvement. In addition, the data to guide therapy in metastatic disease are limited due to the paucity of these tumors. Here, we review the current advances in the management of ANENs within the context of a multidisciplinary approach to these tumors.
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Affiliation(s)
- Amr Mohamed
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sulin Wu
- Department of Internal Medicine, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
- Department of Medical Genetics, Center for Human Genetics, Case Western Reserve University, Cleveland, OH 44106, USA
| | - Mohamed Hamid
- Department of Stem Cell Biology and Regenerative Medicine, City of Hope Beckman Research Institute, Duarte, CA 91010, USA
| | - Amit Mahipal
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sakti Cjakrabarti
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - David Bajor
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - J. Eva Selfridge
- Division of Hematology and Medical Oncology, UH Seidman Cancer Center, 11100 Euclid Avenue, Cleveland, OH 44106, USA
| | - Sylvia L. Asa
- Department of Pathology, UH Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA
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16
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Nikolic AL, Gullifer J, Johnson MA, Hii MW. Oesophageal neuroendocrine tumours-case series of a rare malignancy. J Surg Case Rep 2022; 2022:rjac582. [PMID: 36570553 PMCID: PMC9769948 DOI: 10.1093/jscr/rjac582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 11/26/2022] [Indexed: 12/24/2022] Open
Abstract
Oesophageal neuroendocrine neoplasms (NENs) are rare tumours. Neuroendocrine carcinomas (NECs) are the highest grade of NENs, with aggressive biological behaviour and poor outcomes. No standardized treatment pathways exist for these tumours, with management being individualized based on patient and tumour factors. We present five cases, four men and one women between 63 and 68 years old, who were diagnosed with symptomatic primary oesophageal NECs. Three were diagnosed with localized disease, and two were diagnosed with metastatic disease. Endoscopy, biopsy and staging scan results are outlined. Two patients received neoadjuvant chemotherapy. Three patients with localized disease underwent oesophagectomy. Two of these patients received neoadjuvant chemotherapy. Four patients have succumbed to their disease, with a median survival following a diagnosis of 18 months (5-34 months). This case series highlights the variability of presentation and stage at diagnosis of oesophageal NECs. Multimodal treatment is commonly utilized; however, outcomes are universally poor. Further research is required to determine the optimal treatment regimen for oesophageal NENS.
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Affiliation(s)
- Amanda L Nikolic
- Correspondence address. St Vincent’s Public Hospital Melbourne, 41 Victoria Parade, Fitzroy 3065, Australia. E-mail:
| | - James Gullifer
- Department of Anatomical Pathology, St Vincent’s Hospital Melbourne, Fitzroy 3065, Australia
| | - Mary Ann Johnson
- Department of Hepatobiliary and Upper Gastrointestinal Surgery, St Vincent’s Hospital Melbourne, Fitzroy 3065, Australia
| | - Michael W Hii
- Department of Hepatobiliary and Upper Gastrointestinal Surgery, St Vincent’s Hospital Melbourne, Fitzroy 3065, Australia,The University of Melbourne, Department of Surgery, St Vincent’s Hospital Melbourne, Fitzroy 3065, Australia
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17
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Miyaguchi K, Kawasaki T, Tashima T, Ryozawa S. Mixed neuroendocrine–non‐neuroendocrine neoplasm arising from long‐segment Barrettʼs esophagus showing exceptionally aggressive clinical behavior. Cancer Rep (Hoboken) 2022; 5:e1644. [PMID: 35801304 PMCID: PMC9458485 DOI: 10.1002/cnr2.1644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 04/29/2022] [Accepted: 05/12/2022] [Indexed: 11/08/2022] Open
Abstract
Background Case Conclusion
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Affiliation(s)
- Kazuya Miyaguchi
- Department of Gastroenterology Saitama Medical University International Medical Center Saitama Japan
| | - Tomonori Kawasaki
- Department of Pathology Saitama Medical University International Medical Center Saitama Japan
| | - Tomoaki Tashima
- Department of Gastroenterology Saitama Medical University International Medical Center Saitama Japan
| | - Shomei Ryozawa
- Department of Gastroenterology Saitama Medical University International Medical Center Saitama Japan
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18
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Gushima R, Miyamoto H, Imamura M, Sonoda T, Matsuno K, Yamasaki A, Furuta Y, Hashigo S, Tateyama M, Naoe H, Tanaka Y. Mixed Neuroendocrine Non-Neuroendocrine Neoplasm Arising in the Ectopic Gastric Mucosa of Esophagus. Case Rep Gastroenterol 2022; 16:637-645. [PMID: 36605731 PMCID: PMC9808311 DOI: 10.1159/000527699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 10/12/2022] [Indexed: 12/12/2022] Open
Abstract
Esophageal neuroendocrine neoplasms are extremely rare, and their prognosis is poor. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are even more rare and are defined as tumors consisting of neuroendocrine carcinoma and either adenocarcinoma or squamous cell carcinoma. We report a rare case featuring endoscopic submucosal dissection (ESD) for an esophageal MiNEN, arising from the ectopic gastric mucosa in the lower thoracic esophagus. A 92-year-old male patient was referred to this hospital for investigation of an esophageal tumor. An endoscopic examination revealed a 10 mm elevated lesion, with 8 mm flat areas on the anal side, within the ectopic gastric mucosa located in the lower thoracic esophagus. ESD was carried out, and a histopathological examination revealed a tubular adenocarcinoma composed of differentiated neuroendocrine cells. Immunohistochemical staining was positive for synaptophysin and negative for chromogranin A. The labeling index of Ki-67 was more than 80%. Based on these results, we diagnosed the lesion as an esophageal MiNEN, arising in the ectopic gastric mucosa of the esophagus. The patient remains alive, without recurrence of cancer, 24 months after ESD.
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Affiliation(s)
- Ryosuke Gushima
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideaki Miyamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Miyuki Imamura
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Takayoshi Sonoda
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Kenshi Matsuno
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Akira Yamasaki
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yoki Furuta
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Shunpei Hashigo
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Masakuni Tateyama
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Hideaki Naoe
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Hepatology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
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19
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Wang Y, Huang B, Fu Q, Wang J, Ye M, Hu M, Qu K, Liu K, Hu X, Wei S, Sun K, Xiao W, Zhang B, Li H, Li J, Zhang Q, Liang T. Comprehensive Clinical Analysis of Gallbladder Neuroendocrine Neoplasms: A Large-Volume Multicenter Study During One Decade. Ann Surg Oncol 2022; 29:7619-7630. [PMID: 35849293 DOI: 10.1245/s10434-022-12107-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Accepted: 06/05/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND This study aimed to comprehensively investigate the clinicopathologic characteristics and therapeutic situations of gallbladder neuroendocrine neoplasms (GB-NENs) in the real world via a multicenter, large-scale cohort study. METHODS The study searched for patients in 143 hospitals in China and enrolled 154 patients with GB-NENs diagnosed in 40 hospitals between 2004 and 2021. Clinicopathologic characteristics and therapeutic approaches were analyzed retrospectively. RESULTS The median age at the initial diagnosis of the patients with GB-NENs was 63 years (range 33-83 years), and 61.7% of the patients were women. Tumor-node-metastasis staging classified 92 patients as stage 3 or above. Based on the 2019 World Health Organization classification, 96 cases (62.3%) were confirmed pathologically as poorly differentiated neuroendocrine carcinomas, 13 cases (8.4%) as well-differentiated neuroendocrine tumors, and 45 cases as mixed neuroendocrine-non-neuroendocrine neoplasms. The liver was the most frequent metastatic site. Immunohistochemistry showed that synaptophysin was most frequently positive (80.4%), followed by chromogranin A (61.7%), and CD56 (58.4%). Computed tomography and magnetic resonance imaging showed more common clear boundaries (25/39 cases) and invasive growth features (27 cases). None of these cases had an accurate diagnosis before surgery, with a misdiagnosis rate of 100%. Surgical resection is the main treatment, and platinum-based chemotherapeutic regimens were preferred as adjuvant therapies for patients with GB-NENs. The available survival data for 74 patients showed an overall survival rate of 59% at 1 year, 33% at 3 years, and 29% at 5 years. No significant difference was found between the patients treated with and those treated without adjuvant chemotherapy. CONCLUSIONS Gallbladder neuroendocrine neoplasms have high malignancy and a poor prognosis. Importantly, this large-scale cohort study significantly improves our understanding of GB-NENs and will benefit the exploration of its mechanism and treatment modes. Further investigation is necessary to explore the management of this disease.
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Affiliation(s)
- Yangyang Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Bingfeng Huang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qihan Fu
- Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China.,Zhejiang University Cancer Center, Hangzhou, China.,Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianing Wang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mao Ye
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Manyi Hu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Kai Qu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Kai Liu
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China
| | - Xiao Hu
- Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shumei Wei
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ke Sun
- Department of Pathology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenbo Xiao
- Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Bo Zhang
- Department of General Surgery, Shenzhen University Luohu People's Hospital, Shenzhen, China
| | - Haijun Li
- Department of General Surgery, Shenzhen University Luohu People's Hospital, Shenzhen, China
| | - Jingsong Li
- The Engineering Research Center of EMR and Intelligent Expert System, Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.,Research Center for Healthcare Data Science, Zhejiang Lab, Hangzhou, China
| | - Qi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. .,Zhejiang University Cancer Center, Hangzhou, China.
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. .,Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. .,Zhejiang University Cancer Center, Hangzhou, China.
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20
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Chen C, Hu H, Zheng Z, Yang Y, Chen W, Qiao X, Li P, Zhang S. Clinical characteristics, prognostic factors, and survival trends in esophageal neuroendocrine carcinomas: A population-based study. Cancer Med 2022; 11:4935-4945. [PMID: 35596661 PMCID: PMC9761068 DOI: 10.1002/cam4.4829] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 04/14/2022] [Accepted: 05/01/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare type of malignancy. Clinical data of ENEC are limited to case reports and case series. More information is needed on its clinical feature, management, and prognosis. METHODS This study collected information of ENEC patients diagnosed pathologically from 2010 to 2018. Data including demographic information, clinical features, and survival trends were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analyses were performed with STATA/SE 15.1, SPSS 25.0, and GraphPad Prism 8. RESULTS A total of 283 ENEC patients were included in this study. The small-cell and large-cell subtypes of ENEC possess similar clinical features. The lower third of the esophagus (58%) was the most common location of ENEC. At the time of diagnosis, most ENEC patients were AJCC 7th stage IV (48.1%). Metastasis occurred in more than half of the ENEC patients (53.4%), and the most common metastatic site was the liver (37.1%). Compared with poorly differentiated esophageal squamous cell carcinoma (ESCC), another aggressive malignancy of the esophagus sometimes confused with ENEC because of similar histological features, our study showed differences in tumor location and metastatic rate, but similar poor survival rates. Multivariate survival analysis showed that ENEC located at the middle third of esophagus (p = 0.013), "Brain metastasis" (p = 0.019), and "Liver metastasis" (p < 0.001) were independent predictors of worse outcomes. "Surgery" (p = 0.003), and "Chemotherapy" (p < 0.001) were associated with better survival. CONCLUSION A significant proportion of patients with newly diagnosed ENEC presented with metastatic disease. Predictors of poor survival included tumor location, brain metastasis, and liver metastasis. ENEC and poorly differentiated ESCC share certain histological features, but differ in tumor location and metastatic rate. Yet, no standard treatment strategy has been established, but surgery and chemotherapy were related to better outcomes.
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Affiliation(s)
- Chuyan Chen
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive DiseaseNational Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical UniversityBeijingChina
| | - Haiyi Hu
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive DiseaseNational Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical UniversityBeijingChina
| | - Zhibo Zheng
- Department of International Medical ServicesPeking Union Medical College Hospital, Chinese Academy of Medical SciencesBeijingChina,Department of Thoracic SurgeryPeking Union Medical College Hospital, Chinese Academy of Medical SciencesBeijingChina
| | - Yi Yang
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive DiseaseNational Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical UniversityBeijingChina
| | - Wei Chen
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive DiseaseNational Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical UniversityBeijingChina
| | - Xinwei Qiao
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive DiseaseNational Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical UniversityBeijingChina
| | - Peng Li
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive DiseaseNational Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical UniversityBeijingChina
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive DiseaseNational Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical UniversityBeijingChina
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21
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Holmager P, Langer SW, Kjaer A, Ringholm L, Garbyal RS, Pommergaard HC, Hansen CP, Federspiel B, Andreassen M, Knigge U. Surgery in Patients with Gastro-Entero-Pancreatic Neuroendocrine Carcinomas, Neuroendocrine Tumors G3 and High Grade Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms. Curr Treat Options Oncol 2022; 23:806-817. [PMID: 35362798 DOI: 10.1007/s11864-022-00969-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/16/2022] [Indexed: 12/19/2022]
Abstract
OPINION STATEMENT In the 2019 WHO guidelines, the classification of gastro-entero-pancreatic neuroendocrine neoplasms (GEP NEN) has changed from one being based on Ki-67 proliferation index alone to one that also includes tumor differentiation. Consequently, GEP NENs are now classified as well-differentiated neuroendocrine tumor (NET), NET G1 (Ki-67 <3%), NET G2 (Ki-67 3-20%) and NET G3 (Ki-67 >20%), and poorly differentiated neuroendocrine carcinoma (NEC) (Ki-67 >20%). It has been suggested that NET G3 should be treated as NET G2 with respect to surgery, while surgical management of NEC should be expanded from local disease to also include patients with advanced disease where curative surgery is possible. High grade mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) have a neuroendocrine and a non-neuroendocrine component mostly with a poor prognosis. All studies evaluating the effect of surgery in NEC and MiNEN are observational and hold a risk of selection bias, which may overestimate the beneficial effect of surgery. Further, only a few studies on the effect of surgery in MiNEN exist. This review aims to summarize the data on the outcome of surgery in patients with GEP NET G3, GEP NEC and high grade MiNEN. The current evidence suggests that patients with NEN G3 and localized disease and NEN G3 patients with metastatic disease where curative surgery can be achieved may benefit from surgery. In patients with MiNEN, it is currently not possible to evaluate on the potential beneficial effect of surgery due to the low number of studies.
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Affiliation(s)
- Pernille Holmager
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark. .,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark.
| | - Seppo W Langer
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Oncology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Andreas Kjaer
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Lene Ringholm
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark
| | - Rajendra Singh Garbyal
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Pathology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Hans-Christian Pommergaard
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Surgery and Transplantation, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Carsten Palnæs Hansen
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Surgery and Transplantation, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
| | - Birgitte Federspiel
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mikkel Andreassen
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.,Department of Endocrinology and Metabolism, Copenhagen University Hospital-Rigshospitalet, Ole Maaløes Vej 24, DK-2200, Copenhagen, Denmark.,Department of Surgery and Transplantation, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
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Umar Z, Ilyas U, Otusile I, Landry I. Large-Cell Esophageal Neuroendocrine Tumor Leading to Hepatorenal Syndrome. Cureus 2022; 14:e23720. [PMID: 35509743 PMCID: PMC9060759 DOI: 10.7759/cureus.23720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/01/2022] [Indexed: 11/05/2022] Open
Abstract
Neuroendocrine tumors are tumors that arise from the enterochromaffin cells in the neuroendocrine tissue found throughout the body, particularly the digestive tract, pancreas, and thymus. Neuroendocrine tumors of the esophagus are extremely rare and highly aggressive in nature. We present the case of a 55-year-old Hispanic male who initially presented to the emergency department with right-sided abdominal pain. Imaging revealed innumerable lesions occupying half of the liver parenchyma. Subsequent endoscopy with biopsy of the esophageal and liver lesions along with immunohistochemistry staining was suggestive of a large cell neuroendocrine tumor. He later presented with generalized weakness and right-sided abdominal pain with worsening hepatic and renal function. Over the course of the patient's stay in the hospital, his mental status progressively deteriorated. Given the deranged hepatic and renal function, chemotherapy could not be initiated. The patient's family decided against hemodialysis considering his poor prognosis and the patient expired on day 15 of admission. The case report highlights the aggressiveness of one of the rare esophageal malignancies. It is crucial to establish diagnosis at the earlier stages of the disease with prompt treatment in order to avoid serious complications such as hepatorenal syndrome, which resulted in rapid deterioration of our patient's clinical status. More research is necessary in order to establish guidelines to treat neuroendocrine tumors of the esophagus.
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Yang Z. Differential Diagnosis of High-grade Neuroendocrine Neoplasms in the Digestive System. JOURNAL OF CLINICAL AND TRANSLATIONAL PATHOLOGY 2022; 2:18-22. [DOI: 10.14218/jctp.2022.00008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Liu S, Ge X, Gao Z, Zhou Q, Shi Y, Jiang W, Yang M, Sun X. Clinicopathological analysis of 67 cases of esophageal neuroendocrine carcinoma and the effect of postoperative adjuvant therapy on prognosis. Medicine (Baltimore) 2021; 100:e27302. [PMID: 34713821 PMCID: PMC8556034 DOI: 10.1097/md.0000000000027302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Accepted: 09/02/2021] [Indexed: 01/05/2023] Open
Abstract
The clinicopathological properties of esophageal neuroendocrine carcinoma (ENEC) and its optimal therapy have not been widely studied, as the disease is not common. Consequently, we conducted a retrospective study to analyze the clinical features as well as the prognosis of patients with surgically resected ENEC.The clinicopathological data of patients with ENEC who underwent esophagostomy with regional lymphadenectomy at Jiangsu Province People's Hospital and Jiangsu Provincial Tumor Hospital starting January 2008 until December 2014 were collected.Ninety-two cases of ENEC were part of this study. However, only 67 patients were analyzed and followed up. A univariate model for the Cox proportional hazards revealed that prognosis was associated with postoperative adjuvant therapy, age, and lymph node metastasis (P < .05); a multivariate Cox proportional hazards model showed that postoperative adjuvant therapy was a significant independent prognostic factor. Postoperative adjuvant therapy directly affected overall survival, with a significant disparity noted between the groups (P = .022). In this study, patients who received adjuvant therapy had an average time of survival of 39 months (interquartile range: 27.068-50.932 months), while those who did not receive adjuvant therapy had an average survival time of 13 months (interquartile range: 10.129-15.871 months). The survival time was longer in the treated group than in the untreated group (hazard ratio = 0.47; 95% confidence interval: 0.23-0.94; P = .034).ENEC is a heterogeneous tumor with a very poor prognosis. Combining surgery with adjuvant and/or chemotherapy significantly prolongs the survival of patients, and the optimal treatment for ENEC should be determined with future prospective studies.
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Affiliation(s)
- Shenxiang Liu
- Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
- Department of Oncology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Jiangsu, China
| | - Xiaolin Ge
- Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Zhenzhen Gao
- Department of Oncology, The Second Affiliated Hospital of Jiaxing University, Zhe Jiang, China
| | - Qing Zhou
- Department of Oncology, Jiangsu Provincial Tumor Hospital, Jiangsu, China
| | - Yu Shi
- Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
| | - Wangrong Jiang
- Department of Radiotherapy, People's Liberation Army (PLA) 81 Hospital, Jiangsu, China
| | - Min Yang
- Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
- Jiangsu Institute of Nuclear Medicine, Jiangsu, China
| | - Xinchen Sun
- Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Jiangsu, China
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25
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Chen I, Zhang D, Velez M, Kovar S, Liao X. Poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract: A single-institute study of 43 cases. Pathol Res Pract 2021; 226:153614. [PMID: 34555651 DOI: 10.1016/j.prp.2021.153614] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/05/2021] [Accepted: 09/08/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVES To characterize the clinicopathologic and immunohistochemical features of poorly differentiated neuroendocrine carcinomas (NEC) in the gastrointestinal tract. DESIGN A total of 43 cases were identified and reassessed based on modern classification. RESULTS The cohort (27M, 16F; median age: 66 years) included 16 (37%) large cell NEC, 12 (28%) small cell NEC, 5 (12%) NEC not otherwise specified, and 10 (23%) mixed adenoneuroendocrine carcinomas. Tumor predominantly involved the colon (n = 14, 33%), rectum (n = 13, 30%), and esophagus (n = 9, 21%). Immunohistochemically, INSM1 was the most sensitive marker for neuroendocrine differentiation (28/28, 100%), followed by synaptophysin (40/43, 93%), CD56 (22/35, 63%), and chromogranin (18/40, 45%). SATB2, CDX2, CK20, CK7, abnormal p53, and PD-L1 was positive in 21/26 (81%), 26/37 (70%), 11/35 (31%), 10/35 (29%), 19/24 (79%), and 12/23 (52%) cases, respectively. Three of 25 (11%) were mismatch repair protein deficient. Of 21 resected tumors, 19 (90%) were ≥ pT3 and 13 (62%) had nodal metastasis. Twenty-eight (65%) had distant metastasis. The 5-year survival rate was 21%. The prognosis was stage dependent (p < 0.05), but not associated with tumor type, location, or specific immunomarkers. CONCLUSION Gastrointestinal NECs are aggressive neoplasms. INSM1, synaptophysin, and SATB2 are sensitive markers, although not site or tumor type specific.
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Affiliation(s)
- Irene Chen
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Dongwei Zhang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Moises Velez
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Sierra Kovar
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Xiaoyan Liao
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
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Assarzadegan N, Montgomery E. What is New in the 2019 World Health Organization (WHO) Classification of Tumors of the Digestive System: Review of Selected Updates on Neuroendocrine Neoplasms, Appendiceal Tumors, and Molecular Testing. Arch Pathol Lab Med 2021; 145:664-677. [PMID: 32233993 DOI: 10.5858/arpa.2019-0665-ra] [Citation(s) in RCA: 108] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/26/2019] [Indexed: 12/14/2022]
Abstract
CONTEXT.— The 5th edition of the World Health Organization classification of digestive system tumors discusses several advancements and developments in understanding the etiology, pathogenesis, and diagnosis of several digestive tract tumors. OBJECTIVE.— To provide a summary of the updates with a focus on neuroendocrine neoplasms, appendiceal tumors, and the molecular advances in tumors of the digestive system. DATA SOURCES.— English literature and personal experiences. CONCLUSIONS.— Some of the particularly important updates in the 5th edition are the alterations made in the classification of neuroendocrine neoplasms, understanding of pathogenesis of appendiceal tumors and their precursor lesions, and the expanded role of molecular pathology in establishing an accurate diagnosis or predicting prognosis and response to treatment.
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Affiliation(s)
- Naziheh Assarzadegan
- Department of Pathology, the Johns Hopkins University, School of Medicine, Baltimore, Maryland
| | - Elizabeth Montgomery
- Department of Pathology, the Johns Hopkins University, School of Medicine, Baltimore, Maryland
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Nationwide survey of neuroendocrine carcinoma of the esophagus: a multicenter study conducted among institutions accredited by the Japan Esophageal Society. J Gastroenterol 2021; 56:350-359. [PMID: 33582864 DOI: 10.1007/s00535-020-01756-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 11/30/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Esophageal neuroendocrine carcinoma (ENEC) is an extremely rare type of tumor characterized by a high malignant potential, rapid growth, and poor prognosis. Because the standard therapy for ENEC has been poorly defined, we herein aimed to attain a clear view of the current state of treatment for ENEC by performing a large-scale, multicenter study. METHODS We conducted a questionnaire-based, retrospective clinical review of 142 patients with ENEC treated at 37 hospitals accredited by the Japan Esophageal Society from January 2010 to December 2015. RESULTS The most frequent main treatment performed was an operation, followed by chemoradiotherapy, chemotherapy, and endoscopic submucosal dissection. Among the 67 patients who underwent surgery, 28 (19.7%) were not accurately diagnosed with NEC or a combined NEC tumor by pretreatment biopsy. The 5-year overall survival rate of all patients was 33.2%. Among patients with Stages III and IV disease, the prognosis was significantly better in patients who underwent chemoradiotherapy than in patients who underwent other treatments. Among patients with Stages I and II disease, however, there was no difference in survival rates between those who underwent surgery and chemoradiotherapy. CONCLUSIONS This nationwide survey is a valuable report of the current status of treatment of ENEC in a limited number of cases experienced at each participating institution. The survival benefit obtained from surgery was considered to be limited, especially for Stages III and IV ENEC. Accurate pretreatment histological diagnosis is essential to determine the most appropriate treatment strategy for patients with ENEC.
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28
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Zhao K, Huang Z, Si Y, Sun L, Yu J, Meng X. Use of Chemoradiotherapy as a Treatment Option for Patients with Limited-Stage Primary Small Cell Carcinoma of the Esophagus. Cancer Manag Res 2021; 13:613-623. [PMID: 33531834 PMCID: PMC7846826 DOI: 10.2147/cmar.s278914] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 12/25/2020] [Indexed: 12/12/2022] Open
Abstract
Purpose Currently, there are no standard treatments for primary small cell carcinoma of the esophagus (PSCCE), particularly in cases of limited-stage disease. This retrospective study aimed to assess the treatment strategies and the relevant prognostic factors of limited-stage PSCCE (LS-PSCCE). Patients and Methods We retrospectively evaluated 129 patients with LS-PSCCE between June 2009 and December 2018. The χ2 test was performed to examine the frequencies between different groups. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS). Results Through a median follow-up of 23 months, the median OS of all patients was 25.0 months and the median recurrence-free survival (RFS) was 15.0 months. Univariate and multivariate analyses showed that alcohol abuse (p=0.046) and TNM stage (p<0.001) were independent prognostic factors. There was no significant difference in OS and RFS rates between the patients treated with chemoradiotherapy (CRT) and those treated with surgery and chemotherapy with or without radiotherapy (S+CT±RT) (p>0.05). Patients who received concurrent CRT had better OS and RFS than those who received sequential CRT (p<0.05). Postoperative adjuvant RT for high-risk patients can further improve the local control rate but has no significant effect on OS. Conclusion LS-PSCCE patients treated with CRT had similar OS and RFS compared to those treated with S+CT±RT. This study shows that concurrent CRT confers a survival advantage for patients with LS-PSCCE compared to those with sequential CRT.
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Affiliation(s)
- Kaikai Zhao
- Department of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People's Republic of China
| | - Zhaoqin Huang
- Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People's Republic of China
| | - Youjiao Si
- Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, People's Republic of China
| | - Liangchao Sun
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China
| | - Xiangjiao Meng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People's Republic of China
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Preoperatively Treated Diffuse-Type Gastric Adenocarcinoma: Glucose vs. Other Energy Sources Substantially Influence Prognosis and Therapy Response. Cancers (Basel) 2021; 13:cancers13030420. [PMID: 33498613 PMCID: PMC7866002 DOI: 10.3390/cancers13030420] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 01/19/2021] [Accepted: 01/21/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary The diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity of the primary on baseline FDG-PET. Our data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding. Abstract Diffuse type of gastric adenocarcinoma (dGAC) generally confers a poor prognosis compared to intestinal type. Some dGACs are not avid on fluorine-18 fluoro-2-deoxy-D-glucose PET (FDG-PET) while others seem to consume glucose avidly. We analyzed the outcomes based on the avidity (high with standardized uptake value (SUV) > 3.5 or low with SUV ≤ 3.5) of the primary on baseline FDG-PET. We retrospectively selected 111 localized dGAC patients who had baseline FDG-PET (all were treated with preoperative chemotherapy and chemoradiation). FDG-PET avidity was compared with overall survival (OS) and response to therapy. The mean age was 59.4 years and with many females (47.7%). The high-SUV group (58 (52.3%) patients) and the low-SUV group (53 (47.7%) patients) were equally divided. While the median OS for all patients was 49.5 months (95% CI: 38.5–98.8 months), it was 98.0 months (95% CI: 49.5–NE months) for the low-SUV group and 36.0 months for the high-SUV (p = 0.003). While the median DFS for all patients was 38.2 months (95% CI: 27.7–97.6 months), it was 98.0 (95% CI: 36.9–NE months) months for the low-SUV group was and only 27.0 months (95% CI: 15.2–63.2 months) for the high-SUV group (p = 0.005). Clinical responses before surgery were more common in the low-SUV group but overall we observed only 4 pathologic complete responses in 111 patients. Our unique data suggest that if dGACs used glucose as an energy source then the prognosis was very poor while non-glucose sources improved prognosis. Multi-platform (including metabolomics) profiling of dGACs would yield useful biologic understanding.
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Immunohistochemical Staining With Neuroendocrine Markers is Essential in the Diagnosis of Neuroendocrine Neoplasms of the Esophagogastric Junction. Appl Immunohistochem Mol Morphol 2021; 29:454-461. [PMID: 33480601 DOI: 10.1097/pai.0000000000000906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 12/20/2020] [Indexed: 12/13/2022]
Abstract
Neuroendocrine neoplasms (NENs) of the esophagogastric junction (EGJ) are uncommon and the classification of these tumors has been revised several times. Since 2016, at the Department of Pathology, Rigshospitalet, Denmark, all adenocarcinomas and poorly differentiated carcinomas of the EGJ have been stained routinely with the neuroendocrine markers, synaptophysin and chromogranin A, to detect a possible neuroendocrine component. This study aimed to determine if routine immunohistochemical staining is necessary to detect neuroendocrine differentiation of the EGJ tumors by evaluating how often a neuroendocrine component of the tumors was correctly identified or missed on routine hematoxylin and eosin-stained slides, and by evaluating the interobserver agreement among several pathologists. Of 262 cases a NEN was identified in 24 (9.2%). Up to 22.7% of all EGJ NENs would have been missed without routinely performed neuroendocrine staining in all EGJ tumors. The interobserver agreement between 3 pathologists was slight to moderate. In conclusion, immunohistochemical staining with neuroendocrine markers is essential for the diagnosis of NENs, and to detect all NENs, we recommend to perform this routinely on all resected tumors of the EGJ.
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La Rosa S, Uccella S, Rindi G. Neuroendocrine Neoplasms of the Gut. THE SPECTRUM OF NEUROENDOCRINE NEOPLASIA 2021:207-244. [DOI: 10.1007/978-3-030-54391-4_10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Primary Large Cell Neuroendocrine Carcinoma of the Esophagus Disguised as a Food Impaction. ACG Case Rep J 2020; 7:e00384. [PMID: 33062770 PMCID: PMC7535686 DOI: 10.14309/crj.0000000000000384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Accepted: 03/04/2020] [Indexed: 11/17/2022] Open
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Uccella S, La Rosa S. Looking into digestive mixed neuroendocrine - nonneuroendocrine neoplasms: subtypes, prognosis, and predictive factors. Histopathology 2020; 77:700-717. [PMID: 32538468 DOI: 10.1111/his.14178] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Mixed neuroendocrine - nonneuroendocrine neoplasms (MiNENs) of the digestive system represent a challenge for both pathologists and clinicians. Their nomenclature has changed several times, and their diagnostic criteria, classification and clinical behaviour have been matter of debate over the years. Although several attempts have been made to elucidate the pathogenesis and biology of MiNENs, some issues remain open. This review will provide: a historical background that helps in understanding the evolution of the concept and nomenclature of mixed neoplasms; a revision of the knowledge on this topic, including molecular aspects, to give the reader a comprehensive and practical overview on this challenging field of pathology; a focus on the diagnostic criteria and on the determination of prognostic and predictive factors; and a description of the different tumour types in the different sites of origin.
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Affiliation(s)
- Silvia Uccella
- Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese, Italy
| | - Stefano La Rosa
- Institute of Pathology, University Hospital and University of Lausanne, Lausanne, Switzerland
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Neuroendocrine carcinoma arising from Barrett's esophageal adenocarcinoma: a case report. Clin J Gastroenterol 2020; 13:1028-1035. [PMID: 32852724 DOI: 10.1007/s12328-020-01210-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 08/12/2020] [Indexed: 12/12/2022]
Abstract
Neuroendocrine carcinoma in Barrett's esophagus is rare and its developmental mechanisms remain unclear. Neuroendocrine carcinoma arising in Barrett's esophagus with adenocarcinoma was detected at an early stage and resected by endoscopic submucosal dissection. Detailed pathological examination revealed that the neuroendocrine carcinoma originated via differentiation of the preexisting adenocarcinoma. A 79-year-old man presented with a flat protruding lesion in the esophagogastric junction. Esophagogastroduodenoscopy revealed a red flat 10-mm protruding lesion in the Barrett's epithelium and a shallow depression at the distal end. Narrow band imaging with magnification showed that the blood vessels in the protrusion were dilated and meandered irregularly, while those in the depression were small and did not form a network; the blood vessels were missing in some parts of the depression. Well-differentiated adenocarcinoma was diagnosed after analysis of the biopsy specimen of the protrusion, and endoscopic submucosal dissection was performed. The pathological diagnosis was neuroendocrine carcinoma with an adenocarcinoma component.
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Wu IC, Chu YY, Wang YK, Tsai CL, Lin JC, Kuo CH, Shih HY, Chung CS, Hu ML, Sun WC, Wang JP, Wang HP. Clinicopathological features and outcome of esophageal neuroendocrine tumor: A retrospective multicenter survey by the digestive endoscopy society of Taiwan. J Formos Med Assoc 2020; 120:508-514. [PMID: 32600867 DOI: 10.1016/j.jfma.2020.06.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 05/15/2020] [Accepted: 06/21/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND & AIMS Esophageal neuroendocrine tumors (NET) are very rare and mostly carcinomic, carrying poor prognosis. There is still no guideline or consensus on the treatment for esophageal NET. METHODS Patients with histologically-proven esophageal neuroendocrine tumor were recruited from 9 hospitals in Taiwan between 2002 and 2017. Clinical, laboratory, radiological, endoscopic, pathological data, treatment strategies, follow-up periods, and survivals were collected retrospectively. RESULTS In total, 39 esophageal NET were analyzed and 38 were neuroendocrine carcinoma (NEC). Sixteen (41%) patients had mixed components with either adenocarcinoma (N = 9, 23%) or squamous-cell carcinoma (SCC) (N = 7, 18%). 64.1% of the patients experienced dysphagia and ulcerative mass was the most comment endoscopic finding. There was a higher proportion of drinkers (54.1%), betel chewers (21.6%) and smokers (64.9%) among the patients than in the general population in Taiwan. Five patients (12.8%) had been diagnosed with other cancers. Definite chemoradiotherapy (N = 14, 35.9%) and surgery (N = 7, 17.9%) were the major treatment. Patients with Ki-67% above the median level (50%) in the tumors tended to have worse survival (P = 0.06). However, presence of mixed component was not a significant survival predictor in our study (P = 0.56). CONCLUSION Mixed component of an esophageal NET is commonly observed. Staged workup and the principle of treatment can follow that for the common cancer type of esophagus. The risk factors and behaviors of esophageal NEC in Taiwan seem to be similar to that of esophageal SCC.
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Affiliation(s)
- I-Chen Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yin-Yi Chu
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Department of Gastroenterology and Hepatology, New Taipei Municipal TuCheng Hospital and Chang Gung University, New Taipei City, Taiwan
| | - Yao-Kuang Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cho-Lun Tsai
- Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Jung-Chun Lin
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
| | - Hsiang-Yao Shih
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chen-Shuan Chung
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei, Taiwan
| | - Ming-Luen Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Wei-Chih Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veteran General Hospital, Kaohsiung, Taiwan
| | - Jack P Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei City Hospital, Renai Branch, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei, Taiwan.
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Wang H, Chen Y, Pi G, Zhu Y, Yang S, Mei H, Lin Z, Zhang T. Validation and proposed modification of the 8th edition American Joint Committee on Cancer staging system for patients with esophageal neuroendocrine neoplasms: Evaluation of a revised lymph node classification. Oncol Lett 2020; 19:4122-4132. [PMID: 32382351 DOI: 10.3892/ol.2020.11480] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 01/23/2020] [Indexed: 12/22/2022] Open
Abstract
There is currently no universally accepted staging system for esophageal neuroendocrine neoplasms (ENENs). In the present study, patients with ENENs, identified from the Surveillance, Epidemiology, and End Results registry (SEER) (n=191 patients) and the multicentric series (n=51 patients), were stratified to assess the validity of the 8th American Joint Committee on Cancer (AJCC) staging systems, particularly for esophageal squamous cell carcinoma and esophageal adenocarcinoma. The Kaplan-Meier method was used to assess disease-specific survival (DSS), according to the Tumor-Node-Metastasis (TNM) status, and the Cox model was applied to evaluate differences in prognosis after adjustment for potential confounders. For the 8th AJCC staging classifications, only the pathological stage groups (pTNM) conferred increased hazard ratios from stage I to stage IV, with overlaps between adjacent stages. According to the current findings, the regional lymph nodes involvement status other than the current N classification was a significant predictor of DSS. Consequently, a revised N(Nr) classification was proposed and therefore a new TNrM staging system was adopted, for which progressively poorer DSS associated with increasing stage was observed. Moreover, the concordance index with the modified staging system was slightly higher in patients with ENENs from the SEER registry compared with that of the 8th pTNM system. In conclusion, lymph node status, rather than the number of positive lymph nodes, was a marker of poorer DSS and the modified staging system provided an easier and more accurate staging tool. The present results indicate that revisions to the current staging classifications may be improve the assessment of patient prognosis.
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Affiliation(s)
- Haihong Wang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Yaobing Chen
- Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Guoliang Pi
- Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China
| | - Ying Zhu
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Shengli Yang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Hong Mei
- Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Zhenyu Lin
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
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Wang J, He A, Feng Q, Hou P, Wu J, Huang Z, Xiao Z, Sun C, Liao W, Wu L. Gastrointestinal mixed adenoneuroendocrine carcinoma: a population level analysis of epidemiological trends. J Transl Med 2020; 18:128. [PMID: 32169074 PMCID: PMC7071749 DOI: 10.1186/s12967-020-02293-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 03/07/2020] [Indexed: 02/06/2023] Open
Abstract
Background The rise in incidence and mortality of gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC) has not been well focused. The aim of our study was to examine epidemiological trends in incidence and incidence-based (IB) mortality of gastrointestinal MANEC at a population level. Methods The incidence and IB mortality of gastrointestinal MANEC as well as data on affected patients from 2000 to 2016 were obtained from the Surveillance, Epidemiology, and End Results database. Trends in incidence and IB mortality were assessed using Joinpoint regression. The Kaplan–Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression was used to identify independent predictors of mortality. Results 581 patients diagnosed with gastrointestinal MANEC were enrolled. Gastrointestinal MANEC incidence was 0.23 cases per 1,000,000 individuals in 2000 and 1.16 cases per 1,000,000 individuals in 2016, with an annual percent change (APC) of 8.0% (95% CI 5.7–10.3%, P < 0.05). IB mortality also showed a sustained increase (APC 12.9%, 95% CI 9.0–16.8%, P < 0.05). In Cox regression analysis, age at diagnosis, tumor grade and stage, lymph node metastasis, surgery, and tumor size were independently associated with mortality. Median survival was 75 months (95% CI 60–128 months). Median survival of appendiceal MANEC was significantly longer than that of cecal MANEC (115 vs. 31 months; P < 0.001). Conclusions We found a sustained and rapid increase both in incidence and IB mortality of gastrointestinal MANEC, manifesting that there has been no significant improvement in patient outcomes, nor progress in prevention and treatment. Additional resources should be devoted to gastrointestinal MANEC research.
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Affiliation(s)
- Jiakun Wang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Aoxiao He
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Qian Feng
- Department of Emergency, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Ping Hou
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Junjun Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Zhihao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Zhouqing Xiao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Chi Sun
- Department of Nursing, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China
| | - Wenjun Liao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China.
| | - Linquan Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1, Minde Road, Nanchang, 330006, China.
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Patel B, Klazynski B, Arora SP. High-Grade Large Cell Neuroendocrine Carcinoma: Case Report and Literature Review. J Gastrointest Cancer 2020; 51:341-343. [PMID: 31254245 DOI: 10.1007/s12029-019-00267-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Affiliation(s)
- Bindiya Patel
- Mays Cancer Center, University of Texas Health San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA
| | - Brian Klazynski
- Mays Cancer Center, University of Texas Health San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA
| | - Sukeshi Patel Arora
- Mays Cancer Center, University of Texas Health San Antonio, 7979 Wurzbach Rd, MC8026, San Antonio, TX, 78229, USA.
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Yuan G, Zhan C, Zhu D, Xie H, Wei T, Lu T, Yang Y, Zhu Y, Wang Q. Population-based analysis of esophageal large cell neuroendocrine carcinoma between 2004 and 2015. J Thorac Dis 2020; 11:5480-5488. [PMID: 32030267 DOI: 10.21037/jtd.2019.11.34] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Esophageal large cell neuroendocrine carcinoma (ELCNC) seems a rarely gastrointestinal malignancy. By far, its clinicopathological characteristics and prognosis have not been deeply studied. Methods The data of patients having ELCNC was extracted from the Surveillance, Epidemiology, and End Results (SEER) database, then assessed and compared with information from patients with esophageal small cell neuroendocrine carcinoma (ESCNC) or esophageal squamous cell carcinoma (ESCC). We used univariate and multivariate analyses to accurately detect independent prognostic factors. Results The data of 36 patients for ELCNC were obtained between 2004 and 2015. Compared with patients with ESCNC and ESCC, the mean survival time of ECLNC patients was worse than those with ESCC, while similar to ESCNC. Thus, ELCNC had significantly different clinicopathological characteristics compared to ESCNC and ESCC. Univariate and multivariate analyses revealed that age (P=0.001) and M stage (P=0.004) were independent prognostic factors. Conclusions ELCNC is a rare subtype of esophageal neuroendocrine carcinoma. The clinicopathological features differ from those of other esophageal carcinomas. Prognosis may be closely related to age and M stage.
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Affiliation(s)
- Guangda Yuan
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
| | - Cheng Zhan
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Donglin Zhu
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
| | - Hongya Xie
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
| | - Tengteng Wei
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
| | - Tao Lu
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China
| | - Yong Yang
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
| | - Yimeng Zhu
- Department of Thoracic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China
| | - Qun Wang
- Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai 200032, China
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Treatment strategies for neuroendocrine carcinoma of the upper digestive tract. Int J Clin Oncol 2020; 25:842-850. [PMID: 32036480 DOI: 10.1007/s10147-020-01631-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 01/30/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Neuroendocrine carcinoma (NEC) of the esophagus and the stomach is aggressive. The purpose of this study was to determine the optimal therapeutic strategy. METHODS Both clinicopathological factors and treatment results were examined in 34 patients with immunohistochemically diagnosed NEC of the upper gastrointestinal tract (esophagus 22; stomach 12). RESULTS Twenty-nine tumors showed protruding and localized type, like submucosal tumor. Esophagectomy and gastrectomy were performed in six and eight patients, respectively. Among the six patients with esophageal NEC, three with node metastasis developed recurrence within seven months, while the other three (pT1bN0) had no recurrence. Regarding gastric NEC, three patients with pT3N1 or 2 tumor received adjuvant chemotherapy and achieved a 5-year survival. However, the other five experienced recurrence after gastrectomy. Systemic chemotherapy was performed as the main treatment for 18 patients with advanced NEC. The median survival was 10 months after initial chemotherapy. No marked differences in the response were recognized between the 14 cases with esophageal NEC and the 4 with gastric NEC. The median survival was 14.3 and 5.3 months for the 11 effective and 7 non-effective patients, respectively. CONCLUSIONS A macroscopically unique appearance, like submucosal tumor, suggests the possibility of NEC. Esophagectomy is an effective treatment option for limited-stage NEC without node metastasis, while gastrectomy followed by adjuvant chemotherapy may be effective for NEC even with node metastasis when R0 resection can be achieved. Systemic chemotherapy is relatively effective for advanced NEC, although early progression frequently develops.
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Bellizzi AM. Immunohistochemistry in the diagnosis and classification of neuroendocrine neoplasms: what can brown do for you? Hum Pathol 2020; 96:8-33. [PMID: 31857137 PMCID: PMC7177196 DOI: 10.1016/j.humpath.2019.12.002] [Citation(s) in RCA: 127] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 12/08/2019] [Indexed: 02/07/2023]
Abstract
This review is based on a presentation given at the Hans Popper Hepatopathology Society companion meeting at the 2019 United States and Canadian Academy of Pathology Annual Meeting. It presents updates on the diagnosis and classification of neuroendocrine neoplasms, with an emphasis on the role of immunohistochemistry. Neuroendocrine neoplasms often present in liver biopsies as metastases of occult origin. Specific topics covered include 1. general features of neuroendocrine neoplasms, 2. general neuroendocrine marker immunohistochemistry, with discussion of the emerging marker INSM1, 3. non-small cell carcinoma with (occult) neuroendocrine differentiation, 4. the WHO Classification of neuroendocrine neoplasms, with discussion of the 2019 classification of gastroenteropancreatic neoplasms, 5. use of Ki-67 immunohistochemistry, 6. immunohistochemistry to assign site of origin in neuroendocrine metastasis of occult origin, 7. immunohistochemistry to distinguish well-differentiated neuroendocrine tumor G3 from poorly differentiated neuroendocrine carcinoma, 8. lesions frequently misdiagnosed as well-differentiated neuroendocrine tumor, and 9. required and recommended data elements for biopsies and resections with associated immunohistochemical stains. Next-generation immunohistochemistry, including lineage-restricted transcription factors (e.g., CDX2, islet 1, OTP, SATB2) and protein correlates of molecular genetic events (e.g., p53, Rb), is indispensable for the accurate diagnosis and classification of these neoplasms.
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Affiliation(s)
- Andrew M Bellizzi
- Department of Pathology, University of Iowa Hospitals and Clinics and Carver College of Medicine, Iowa City, IA, USA; University of Iowa Neuroendocrine Cancer Program, University of Iowa Hospitals and Clinics and Holden Comprehensive Cancer Center, Iowa City, IA 52242, USA.
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Taggart MW, Foo WC, Lee SM. Tumors of the Gastrointestinal System Including the Pancreas. ONCOLOGICAL SURGICAL PATHOLOGY 2020:691-870. [DOI: 10.1007/978-3-319-96681-6_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Shi H, Qi C, Meng L, Yao H, Jiang C, Fan M, Pang S, Zhang Q, Lin R. Do neuroendocrine carcinomas and mixed neuroendocrine-non-neuroendocrine neoplasm of the gastrointestinal tract have the same prognosis? A SEER database analysis of 12,878 cases. Ther Adv Endocrinol Metab 2020; 11:2042018820938304. [PMID: 32670540 PMCID: PMC7338725 DOI: 10.1177/2042018820938304] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 06/08/2020] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Neuroendocrine carcinomas (NECs) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) in the gastrointestinal (GI) tract are both rare and malignant; however, it is unclear whether their prognosis is the same. METHODS In this cross-sectional study, a total of 12,878 patients with NEC or MiNEN in the GI tract were reviewed retrospectively by searching the Surveillance, Epidemiology, and End Results (SEER) program database. Next, we compared the characteristics and survival between patients with NEC or MiNEN and further analyzed the prognostic factors for the patients. RESULTS The data showed that patients with MiNEN had a worse prognosis as compared with patients with pure NEC in the small intestine (SI) and appendix, whereas there was no significant survival difference between NEC and MiNEN in the other parts of the GI system. On the whole, age ⩾55 years (p < 0.0001), male (p = 0.002), being diagnosed at TNM Stage II-IV (p < 0.0001) or not receiving surgical treatment (p < 0.0001) were the independent negative prognostic factors for NEC patients, whereas age ⩾55 years (p = 0.003), being diagnosed at TNM Stage III-IV (p < 0.001) or not receiving surgical treatment (p < 0.001) were identified as the independent negative prognostic factors for the MiNEN patients. Furthermore, when NECs or MiNENs were classified based on the primary tumor site, the results showed that the prognostic factors for NEC and MiNEN varied between the tumor sites. CONCLUSION The prognostic differences between NECs and MiNENs in the GI tract are heterogeneous and site-related. Patients with appendiceal or SI MiNEN have a poorer prognosis than patients with pure appendiceal or SI NEC. Therefore, we should pay more attention to patients with MiNEN in the SI and appendix and monitor them more closely.
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Affiliation(s)
| | | | - Lingjun Meng
- Department of Gastroenterology, Union Hospital,
Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China
| | - Hailing Yao
- Department of Gastroenterology, Union Hospital,
Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China
| | - Chen Jiang
- Department of Gastroenterology, Union Hospital,
Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China
| | - Mengke Fan
- Department of Gastroenterology, Union Hospital,
Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China
| | - Suya Pang
- Department of Gastroenterology, Union Hospital,
Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, China
| | - Qin Zhang
- Department of Pathology, Union Hospital, Tongji
Medical College, Huazhong University of Science and Technology, Wuhan,
China
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Zhang G, Wu B, Wang X, Li J. A competing-risks nomogram and recursive partitioning analysis for cause-specific mortality in patients with esophageal neuroendocrine carcinoma. Dis Esophagus 2019; 32:5304731. [PMID: 30715226 DOI: 10.1093/dote/doy129] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Indexed: 12/11/2022]
Abstract
The objective of this study is to estimate the probability of cause-specific mortality using a competing-risks nomogram and recursive partitioning analysis in a large population-based cohort of patients with esophageal neuroendocrine carcinoma. The surveillance, epidemiology and end results database was used to identify 162 patients diagnosed with esophageal neuroendocrine carcinoma from 1998 to 2014. We estimated a cumulative incidence function for cause-specific mortality. A nomogram was constructed by using a proportional subdistribution hazard model, validated using bootstrap cross-validation, and evaluated with a decision curve analysis to assess its clinical utility. Finally, we performed risk stratification using a recursive partitioning analysis to divide patients with esophageal neuroendocrine carcinoma into clinically useful prognostic groups. Tumor location, distant metastasis, surgery, radiotherapy, and chemotherapy were significantly associated with cause-specific mortality. The calibration plots demonstrated good concordance between the predicted and actual outcomes. The discrimination performance of a Fine-Gray model was evaluated by using the c-index, which was 0.723 for cause-specific mortality. The decision curve analysis ranged from 0.268 to 0.968 for the threshold probability at which the risk model provided net clinical benefits relative to hypothetical all-screening and no-screening scenarios. The risk groups stratified by a recursive partitioning analysis allowed significant distinction between cumulative incidence curves. We determined the probability of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and developed a nomogram and recursive partitioning analysis stratification system based on a competing-risks model. The nomogram and recursive partitioning analysis appear to be suitable for risk stratification of cause-specific mortality in patients with esophageal neuroendocrine carcinoma and will help clinicians to identify patients at increased risk of cause-specific mortality to guide treatment and surveillance decisions.
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Affiliation(s)
- G Zhang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - B Wu
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - X Wang
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
| | - J Li
- Department of Thoracic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
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Ye L, Lu H, Wu L, Zhang L, Shi H, Wu HM, Tu P, Li DM, Wang FY. The clinicopathologic features and prognosis of esophageal neuroendocrine carcinomas: a single-center study of 53 resection cases. BMC Cancer 2019; 19:1234. [PMID: 31852479 PMCID: PMC6921601 DOI: 10.1186/s12885-019-6420-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 12/01/2019] [Indexed: 01/08/2023] Open
Abstract
Background Esophageal neuroendocrine carcinomas (NECs) are exceedingly rare and poorly understood. The aims of the retrospective study were to delineate the clinicopathologic features and prognosis of patients with the disease. Methods We performed a retrospective study containing 53 patients of esophageal NECs in our center from 2002 through 2018. Patients were assigned to the pure esophageal NECs group and the esophageal NECs mixed with squamous carcinoma and/or esophageal adenocarcinoma (MiNECs) group. Demographic, clinical, pathologic and prognostic factors were recorded and analyzed. Results Of the 53 patients, elderly male patients were predominant. Dysphagia was the most common symptom (45/53, 84.9%). Most tumors were centered in the middle esophagus (36/53,67.9%).Ulcerated appearance was frequently seen in the pure NECs (56.8%), and the tumors in the MiNECs group mostly represented elevated types (57.9%). Synaptophysin (38/45, 84.4%), chromogranin A (21/38, 55.3%) and CD56(23/27, 85.2%) have been proven to be positive markers for NECs. Most patients (46/53, 86.8%) received surgery combined with chemotherapy. Though the pathologic stages were alike (P = 0.129), the median survival time was 3.53 years for the pure NECs group and 7 years for the MiNECs group. In multivariate analysis, pathologic stage (RR = 1.938, P = 0.045) and age (RR = 2.410, P = 0.028) were independent prognostic factors for patients with MiNECs. The prognosis of patients with pure NECs was independent from any factors. Conclusions Careful endoscopic examination could help distinguish pure NECs from MiNECs. NECs were aggressive, but a relative better prognosis for patients with MiNECs. Surgery should be performed if applicable, and chemotherapy might be helpful.
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Affiliation(s)
- Lei Ye
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China
| | - Heng Lu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China
| | - Lin Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China
| | - Lei Zhang
- Department of cardiothoracic surgery, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China
| | - Hui Shi
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China
| | - Hui Min Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China
| | - Pin Tu
- Department of Pathology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China
| | - De Min Li
- Department of cardiothoracic surgery, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China.
| | - Fang Yu Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China.
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Paired Box 5 (PAX5) Expression in Poorly Differentiated Neuroendocrine Carcinoma of the Gastrointestinal and Pancreatobiliary Tract: Diagnostic and Potentially Therapeutic Implications. Appl Immunohistochem Mol Morphol 2019; 26:545-551. [PMID: 27941564 DOI: 10.1097/pai.0000000000000473] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Paired Box 5 (PAX5), a well-established B-cell marker, is preferentially expressed in small cell lung carcinoma and regulates the transcription of c-Met, offering a potential for therapeutic target. Its expression in poorly differentiated neuroendocrine carcinoma (PDNEC) of the digestive system has not been systemically evaluated. Archived pathology materials from 38 PDNEC in the gastrointestinal (GI) and pancreatobiliary (PB) tract were reviewed. Representative tumor sections were subject to immunohistochemical stain for PAX5, c-Met, and CD20. The extent of the staining [focal (<10%), patchy (10% to 50%), and diffuse (>50%)] and intensity (1+ to 3+) was evaluated. In total, 38 cases of well-differentiated neuroendocrine tumors from GI/PB tract served as controls. Nuclear PAX5 staining was observed in 16 (42%) cases in total, in 46% (11/24) of large cell neuroendocrine carcinoma, 67% (4/6) of small cell neuroendocrine carcinoma, and 13% (1/8) of mixed adenoneuroendocrine carcinoma, with diffuse (8), patchy (4), or focal (4) staining. The intensity was 3+ (2), 2+ (6), and 1+ (8). PAX5 expression was common in ampullary (4/5) and gastroesophageal junctional/esophageal (5/9) PDNEC. Two (5%) of 38 well-differentiated neuroendocrine tumors were positive for PAX5. Three PAX5 positive PDNEC showed weak cytoplasmic c-Met immunolabeling. CD20 was negative in all tumors. Our data show that PAX5 is commonly expressed in PDNEC of the GI/PB tract including small cell neuroendocrine carcinoma. This observation warrants a cautious approach when interpreting small biopsy of poorly differentiated neoplasms, especially when lymphoma is considered in the differentials. Further study of PAX5/c-Met signaling pathway and its potential therapeutic value in GI/PB PDNEC is warranted.
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Ichimata S, Aoyagi D, Takehana T, Uehara T, Shiozawa S. A case of large cell neuroendocrine carcinoma exhibiting rhabdoid features in the esophagogastric junction. Pathol Int 2019; 69:481-487. [DOI: 10.1111/pin.12807] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 04/10/2019] [Accepted: 04/12/2019] [Indexed: 12/27/2022]
Affiliation(s)
- Shojiro Ichimata
- Department of Laboratory MedicineShinshu University Hospital Matsumoto Japan
- Department of PathologySaku Central Hospital Advanced Care Center Saku Japan
| | - Daiju Aoyagi
- Department of PathologySaku Central Hospital Advanced Care Center Saku Japan
| | - Takuo Takehana
- Department of Gastroenterological SurgerySaku Central Hospital Advanced Care Center Saku Japan
| | - Takeshi Uehara
- Department of Laboratory MedicineShinshu University Hospital Matsumoto Japan
| | - Satoshi Shiozawa
- Department of PathologySaku Central Hospital Advanced Care Center Saku Japan
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Tanaka Y, Hirata D, Fujii S, Kusaka T, Shibuya S. Early-stage Neuroendocrine Carcinoma of the Esophagus Observed with Annual Endoscopy for Three Years. Intern Med 2019; 58:1727-1731. [PMID: 30799355 PMCID: PMC6630144 DOI: 10.2169/internalmedicine.2151-18] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
An 80-year-old man was found to have a reddish depressed lesion on the middle thoracic esophagus. The morphology of the lesion had been almost unchanged for 3 years, but it transformed to a 2-cm depressed lesion with elevated margins and an irregular nodular surface. The lesion was resected endoscopically and ultimately diagnosed as a combined neuroendocrine carcinoma and squamous cell carcinoma with submucosal invasion. The patient was additionally treated with chemoradiotherapy but died of the primary disease eight months after the initial treatment. It is important to elucidate the natural history of this disease at an early stage.
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Affiliation(s)
- Yasuyuki Tanaka
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
| | - Daizen Hirata
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
| | - Shigehiko Fujii
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
| | - Toshihiro Kusaka
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Japan
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49
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Neuroendocrine carcinoma of the esophagus with an adenocarcinoma component. Clin J Gastroenterol 2019; 12:534-538. [PMID: 31134449 DOI: 10.1007/s12328-019-00995-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 05/21/2019] [Indexed: 12/20/2022]
Abstract
A 68-year-old male was referred with dysphagia. Endoscopic findings showed circular stenosis with a protruding mass in the lower esophagus. Biopsy showed adenocarcinoma and there was no evidence of distant metastases. A subtotal esophagectomy was performed. The resected specimen revealed a mixed neuroendocrine carcinoma with adenocarcinoma. The adenocarcinoma component was on the surface of the tumor and the neuroendocrine component invaded the deeper portion. Immunohistochemically, the neuroendocrine carcinoma component stained positive for cytokeratin 7 and cytokeratin 20, suggesting that the neuroendocrine carcinoma originated from the adenocarcinoma. The adenocarcinoma component stained positive for MUC2, which suggests that the adenocarcinoma component originated from Barrett's epithelium. Taken together, the neuroendocrine carcinoma may have originated from Barrett's epithelium. A metastasis to the liver was found 2 months after the surgical resection. Chemotherapy was administered, but there was no response. Most esophageal neuroendocrine carcinomas are accompanied by adenocarcinoma or squamous cell components, suggesting that these carcinomas originate from pluripotent cells in squamous or Barrett's epithelium. Appropriate chemotherapy for these lesions should be considered based on the cell of origin.
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50
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Mafficini A, Scarpa A. Genetics and Epigenetics of Gastroenteropancreatic Neuroendocrine Neoplasms. Endocr Rev 2019; 40:506-536. [PMID: 30657883 PMCID: PMC6534496 DOI: 10.1210/er.2018-00160] [Citation(s) in RCA: 144] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Accepted: 12/27/2018] [Indexed: 12/11/2022]
Abstract
Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) are heterogeneous regarding site of origin, biological behavior, and malignant potential. There has been a rapid increase in data publication during the last 10 years, mainly driven by high-throughput studies on pancreatic and small intestinal neuroendocrine tumors (NETs). This review summarizes the present knowledge on genetic and epigenetic alterations. We integrated the available information from each compartment to give a pathway-based overview. This provided a summary of the critical alterations sustaining neoplastic cells. It also highlighted similarities and differences across anatomical locations and points that need further investigation. GEP-NENs include well-differentiated NETs and poorly differentiated neuroendocrine carcinomas (NECs). NENs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, NECs are G3 by definition. The distinction between NETs and NECs is also linked to their genetic background, as TP53 and RB1 inactivation in NECs set them apart from NETs. A large number of genetic and epigenetic alterations have been reported. Recurrent changes have been traced back to a reduced number of core pathways, including DNA damage repair, cell cycle regulation, and phosphatidylinositol 3-kinase/mammalian target of rapamycin signaling. In pancreatic tumors, chromatin remodeling/histone methylation and telomere alteration are also affected. However, also owing to the paucity of disease models, further research is necessary to fully integrate and functionalize data on deregulated pathways to recapitulate the large heterogeneity of behaviors displayed by these tumors. This is expected to impact diagnostics, prognostic stratification, and planning of personalized therapy.
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Affiliation(s)
- Andrea Mafficini
- ARC-Net Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.,Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Aldo Scarpa
- ARC-Net Center for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.,Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
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